Clinical Use of N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) in Diagnosing Acute Heart Failure in Emergency Settings: A Systematic Review

Acute heart failure (AHF) is a common emergency department presentation where rapid and accurate diagnosis is challenging. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a widely used biomarker for AHF, but uncertainty remains regarding optimal cut-offs and performance across patient subgroups. This systematic review evaluates the diagnostic utility of NT-proBNP for AHF in emergency settings. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, Scopus, and Web of Science (January 2021-April 2026). Eligible studies enrolled adults with suspected AHF in emergency settings, used NT-proBNP as the index test, and reported diagnostic accuracy outcomes. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A narrative synthesis was performed. Eight studies were included. Across prospective emergency department studies, an NT-proBNP threshold of <300 pg/mL demonstrated strong rule-out performance, with reported sensitivities ranging from 96% to approximately 99% and negative predictive values ranging from 94.8% to 95%, depending on the study population and reference standard. Age-adjusted cut-offs (450/900/1800 pg/mL) produced rule-in specificities of 61-87%. Diagnostic accuracy was significantly reduced in patients with atrial fibrillation (AF), congenital heart disease (CHD), and heart failure with preserved ejection fraction (HFpEF). Five studies had low risk of bias, while three had high risk. NT-proBNP is a highly effective rule-out test for AHF using a <300 pg/mL cut-off. Age-adjusted cut-offs improve rule-in specificity. Performance is attenuated in key subgroups, requiring modified interpretation. Despite some methodological limitations, current evidence strongly supports routine NT-proBNP use in emergency department patients with suspected AHF.